Efforts are presently underway to develop a series of highly lipophilic alkylating agents based on the 2-azaadamantyl system which, in addition to having potential for penetration into the central nervous system, are of rigidly defined stereochemistry. When the system is completed, i.e., when the entire series is available, differential cytotoxicity within the series is expected, based upon the different distances between the alkylating centers and the different directions of approach the nucleophilic sites of DNA must take to react with the substrates. Cytotoxicity and selectivity will be correlated with structure and physicochemical parameters such as rate of reaction, log P, etc. Bioassays will be performed to measure transport of radiolabeled derivatives of a series into rat brain CNS, as well as cytotoxicity testing in KB9 tissue culture.